The object of this contract is to establish parameters for cocaine self- administration in rats which appear to model cocaine addiction in man. Since cocaine addiction is a multifaceted illness with different components (arousal, craving, drug-seeking, drug-taking, reward, abstinence, withdrawal, relapse, and recovery), the basic aim is to further understand each of these behavioral states and attempt to identify paradigms that approximate each of these states. For example, the use of a discrete trials procedure in rats developed by the contractor appears similar to the cyclic nature of drug taking behaviors in man. This may more closely approximate the binging pattern that is often seen in cocaine abusers. The work will involve studying basic neurotransmitter systems in the brain, and will utilize existing drugs and new experimental compounds to alter these transmitter systems. For example, the role of dopamine, serotonin, or other endogenous amines will be investigated. The animal model will utilize the progressive ratio schedule of cocaine self- administration, with a concurrent, sequential, or parallel second reinforcer (a food- or water--maintained schedule) to assess the general condition of the rats. It is anticipated that eight to twelve compounds will be studied each year in each of the several paradigms of the basic model that are designed by the contractor. The compounds will be assigned by the Project Officer.